Period of hospitalization and mortality in transferred versus non-transferred COVID-19 patients: results from Germany

COVID-19 was a challenge for health-care systems worldwide, causing large numbers of hospitalizations and inter-hospital transfers. We studied whether transfer, as well as its reason, was associated with the duration of hospitalization in non-ICU and ICU patients. For this purpose, all patients hospitalized due to COVID-19 between August 1st and December 31st, 2021, in a network of hospitals in Southern Germany were comprehensively characterized regarding their clinical course, therapy, complications, transfers, reasons for transfer, involved levels of care, total period of hospitalization and in-hospital mortality, using univariate and multiple regression analyses. While mortality was not significantly associated with transfer, the period of hospitalization was. In non-ICU patients (n = 545), median (quartiles) time was 7.0 (4.0–11.0) in non-transferred (n = 458) and 18.0 (11.0–29.0) days in transferred (n = 87) patients (p < 0.001). In ICU patients (n = 100 transferred, n = 115 non-transferred) it was 12.0 (8.3–18.0) and 22.0 (15.0–34.0) days (p < 0.001). Beyond ECMO therapy (4.5%), reasons for transfer were medical (33.2%) or capacity (61.9%) reasons, with medical/capacity reasons in 32/49 of non-ICU and 21/74 of ICU patients. Thus, the transfer of COVID-19 patients between hospitals was associated with longer periods of hospitalization, corresponding to greater health care utilization, for which specific patient characteristics and clinical decisions played a role.

Regarding the level of care of the hospitals, 55.0% of transfers involved transfer to a lower level, 38.6% to a higher level, and 6.4% to the same level.Again, the pattern was preserved in subsequent transfers.
We additionally aimed to describe the transfers between hospitals in more detail, as four RoMed hospitals and several other hospitals were involved in the treatment of COVID-19 patients.The Supplemental Table S2 demonstrates that most transfers occurred within the RoMed hospital group, followed by transfers to external clinics.Only 11.4% of transfers occurred as transfers from external clinics into the RoMed group.

Comprehensive analysis of the relationship between period of hospitalization and transfer
In order to disentangle the relationship between patients characteristics, risk factors, transfer and hospital stay and reveal whether the difference associated with transfer would remain robust when including these additional factors, we employed multiple linear regression analysis, using clinically plausible predictors that could have an influence on hospital stay.

Patients without ICU stay
Using transfer as single predictor, this corresponded to a mean prolongation by 12.5 days (p<0.001).
A similar result for the effect of transfer was obtained when patients who died (n=83) were excluded from the analysis.
If the reason of transfer, either medical or capacity-related, was added as predictor, transfer was still significantly linked to the period of hospitalization, with a similar estimate and confidence interval, while the reason was not significant.As the distribution of time was skewed (see Figure 1), the analysis was repeated with a hospital stay winsored at 60 days, as well as with its logarithm.This confirmed transfer as being significantly linked to the period of hospitalization (p<0.001each).

Patients with ICU stay
ECMO patients were excluded from this analysis due to their very specific conditions compared to patients without ECMO.Transfer as single predictor corresponded to a mean prolongation by 11.8 days (p<0.001).The set of additional predictors and the strategy of analysis followed the same approach as in the patients without ICU stay.When using the same additional predictors as in the non-ICU group, transfer remained significant (p=0.048), with a mean (95%CI) effect of 10.5 (0.1; 21.0) days on hospital stay.The period of hospitalization was not associated with any of the other predictors except death (-15.8 (-29.7; -1.8) days; p=0.027).If patients who died (n=63) were excluded from the analysis, transfer was no more significant (p=0.376), with a mean effect of 5.8 (-7.4; 18.9) days.If the reason of transfer was added as predictor, transfer was again significantly linked to hospital stay, with a similar estimate and confidence interval as above, while the reason was not significant.When the analysis was repeated with a hospital stay winsored at 60 days, or with its logarithm, transfer was confirmed as a significant prolongator of stay (p<0.05each).These findings indicated the major role of death regarding the relationship between transfer and hospital stay in patients with ICU stay.From external to external (%) 0 (0.0%) 1 (3.2%)Supplemental Table S3: Causes and characteristics of transfers.Please note that in the present study only the first transfer was analyzed.Subsequent transfers are shown in this table to demonstrate that their percentages were small compared to those of initial transfers.*Two patients were transferred 3 times, which was the maximum number of transfers for a patient.**Includes back transfers to initial hospital (n=7)

Table S1 :
Comorbidities. *Percentages refer to column.Comparisons between groups were performed with Fisher´s exact test, or the Mann-Whitney U-test, depending on the type of variable.*Percentagesreferto the respective column. 1 Comparison between non-transferred patients without any ICU stay and transferred patients without any ICU stay.2Comparison between non-transferred patients with any ICU stay and transferred patients with any ICU stay.Data were available in all 760 patients and percentages refer to this number.ICU patients comprise those with ECMO therapy

Table S2 :
Vital signs and laboratory values as well as pharmacological therapy measures in the different subgroups of patients.sPO2=peripheraloxygensaturation, CRP=C-reactive protein, LDH=lactate dehydrogenase, GPT/ALT=glutamate pyruvate transaminase/alanine transaminase, eGFR=estimated glomerular filtration rate computed from creatinine levels in blood, NT-proBNP= N-terminal pro-B-type natriuretic peptide, IgG=immunoglobulin G. Numbers and percentages (in parentheses) are given, or median values and quartiles (in parentheses), where appropriate.Comparisons between groups were performed with the Mann-Whitney U-test or Fisher´s exact test, depending on the type of variable.*Percentagesreferto the respective column.1Comparisonbetween non-transferred patients without any ICU stay and transferred patients without any ICU stay. 2 Comparison between non-transferred patients with any ICU stay and transferred patients with any ICU stay.ICU patients comprise those with ECMO therapy